211 research outputs found
The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells
The eukaryotic translation initiation factor 2α (eIF2α) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response (ISR). A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally. However, mouse GCN2 activation has recently been observed in circumstances associated with ribosome stalling with no global increase in uncharged tRNAs. We report on a mammalian CHO cell-based CRISPR-Cas9 mutagenesis screen for genes that contribute to ISR activation by amino acid starvation. Disruption of genes encoding components of the ribosome P-stalk, uL10 and P1, selectively attenuated GCN2-mediated ISR activation by amino acid starvation or interference with tRNA charging without affecting the endoplasmic reticulum unfolded protein stress-induced ISR, mediated by the related eIF2α kinase PERK. Wildtype ribosomes isolated from CHO cells, but not those with P-stalk lesions, stimulated GCN2-dependent eIF2α phosphorylation in vitro. These observations support a model whereby lack of a cognate charged tRNA exposes a latent capacity of the ribosome P-stalk to activate GCN2 in cells and help explain the emerging link between ribosome stalling and ISR activation
The Identification of the X-ray Counterpart to PSR J2021+4026
We report the probable identification of the X-ray counterpart to the
gamma-ray pulsar PSR J2021+4026 using imaging with the Chandra X-ray
Observatory ACIS and timing analysis with the Fermi satellite. Given the
statistical and systematic errors, the positions determined by both satellites
are coincident. The X-ray source position is R.A. 20h21m30.733s, Decl. +40 deg
26 min 46.04sec (J2000) with an estimated uncertainty of 1.3 arsec combined
statistical and systematic error. Moreover, both the X-ray to gamma-ray and the
X-ray to optical flux ratios are sensible assuming a neutron star origin for
the X-ray flux. The X-ray source has no cataloged infrared-to-visible
counterpart and, through new observations, we set upper limits to its optical
emission of i' >23.0 mag and r' > 25.2mag. The source exhibits an X-ray
spectrum with most likely both a powerlaw and a thermal component. We also
report on the X-ray and visible light properties of the 43 other sources
detected in our Chandra observation.Comment: Accepted for publication in the Astrophysical Journa
The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells.
The eukaryotic translation initiation factor 2a (eIF2a) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response (ISR). A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally. However, mouse GCN2 activation has recently been observed in circumstances associated with ribosome stalling with no global increase in uncharged tRNAs. We report on a mammalian CHO cell-based CRISPR-Cas9 mutagenesis screen for genes that contribute to ISR activation by amino acid starvation. Disruption of genes encoding components of the ribosome P-stalk, uL10 and P1, selectively attenuated GCN2-mediated ISR activation by amino acid starvation or interference with tRNA charging without affecting the endoplasmic reticulum unfolded protein stress-induced ISR, mediated by the related eIF2a kinase PERK. Wildtype ribosomes isolated from CHO cells, but not those with P-stalk lesions, stimulated GCN2-dependent eIF2a phosphorylation in vitro. These observations support a model whereby lack of a cognate charged tRNA exposes a latent capacity of the ribosome P-stalk to activate GCN2 in cells and help explain the emerging link between ribosome stalling and ISR activation
A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope
Globular clusters with their large populations of millisecond pulsars (MSPs)
are believed to be potential emitters of high-energy gamma-ray emission. Our
goal is to constrain the millisecond pulsar populations in globular clusters
from analysis of gamma-ray observations. We use 546 days of continuous
sky-survey observations obtained with the Large Area Telescope aboard the Fermi
Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular
clusters. Steady point-like high-energy gamma-ray emission has been
significantly detected towards 8 globular clusters. Five of them (47 Tucanae,
Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices and clear evidence for an exponential cut-off in the range
1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission
from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral
indices , however the presence of an exponential cut-off
can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC
6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral
properties. From the observed gamma-ray luminosities, we estimate the total
number of MSPs that is expected to be present in these globular clusters. We
show that our estimates of the MSP population correlate with the stellar
encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters,
commensurate with previous estimates. The observation of high-energy gamma-ray
emission from a globular cluster thus provides a reliable independent method to
assess their millisecond pulsar populations that can be used to make
constraints on the original neutron star X-ray binary population, essential for
understanding the importance of binary systems in slowing the inevitable core
collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J.
Kn\"odlseder, N. Webb, B. Pancraz
The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment
The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in
operation since July 2014. This paper describes the second data release from
this phase, and the fourteenth from SDSS overall (making this, Data Release
Fourteen or DR14). This release makes public data taken by SDSS-IV in its first
two years of operation (July 2014-2016). Like all previous SDSS releases, DR14
is cumulative, including the most recent reductions and calibrations of all
data taken by SDSS since the first phase began operations in 2000. New in DR14
is the first public release of data from the extended Baryon Oscillation
Spectroscopic Survey (eBOSS); the first data from the second phase of the
Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2),
including stellar parameter estimates from an innovative data driven machine
learning algorithm known as "The Cannon"; and almost twice as many data cubes
from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous
release (N = 2812 in total). This paper describes the location and format of
the publicly available data from SDSS-IV surveys. We provide references to the
important technical papers describing how these data have been taken (both
targeting and observation details) and processed for scientific use. The SDSS
website (www.sdss.org) has been updated for this release, and provides links to
data downloads, as well as tutorials and examples of data use. SDSS-IV is
planning to continue to collect astronomical data until 2020, and will be
followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14
happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov
2017 (this is the "post-print" and "post-proofs" version; minor corrections
only from v1, and most of errors found in proofs corrected
Jimmy Swaggart's Secular Confession
This is the author's accepted manuscript. The published version is available from http://dx.doi.org/10.1080/02773940902766748 .Following the exposure of televangelist Jimmy Swaggartâs illicit rendezvous with a New Orleans prostitute, the Assemblies of God simultaneously orchestrated a massive attempt to silence those who would discuss the tryst and arranged the most widely publicized confession in American history theretofore. The coincidence of a âsilence campaignâ with the vast distribution of a public confession invites us to reconsider the nature of the public confession. For what place has a public confession, the discourse of disclosure par excellence, in a silence campaign? This question is best answered, I argue, if we understand public confession not as a stable a-historical form, but as a practice that is informed by multiple, competing traditions. I argue that by situating Swaggartâs performance in a philosophically modern and secular tradition of public confession we can understand both its complicity in a silence campaign and, more generally, the political logic of the modern public confession
The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars
We present 294 pulsars found in GeV data from the Large Area Telescope (LAT)
on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs)
discovered in deep radio searches of LAT sources will likely reveal pulsations
once phase-connected rotation ephemerides are achieved. A further dozen optical
and/or X-ray binary systems co-located with LAT sources also likely harbor
gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and
candidates, 10% of all known pulsars, compared to known before Fermi.
Half of the gamma-ray pulsars are young. Of these, the half that are undetected
in radio have a broader Galactic latitude distribution than the young
radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall,
>235 are bright enough above 50 MeV to fit the pulse profile, the energy
spectrum, or both. For the common two-peaked profiles, the gamma-ray peak
closest to the magnetic pole crossing generally has a softer spectrum. The
spectral energy distributions tend to narrow as the spindown power
decreases to its observed minimum near erg s, approaching the
shape for synchrotron radiation from monoenergetic electrons. We calculate
gamma-ray luminosities when distances are available. Our all-sky gamma-ray
sensitivity map is useful for population syntheses. The electronic catalog
version provides gamma-ray pulsar ephemerides, properties and fit results to
guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen
THE CONCISE GUIDE TO PHARMACOLOGY 2019/20 : G protein- coupled receptors
The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.Peer reviewe
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